The production of novel chimeric receptor proteins which initiate signaling in a cell that results in activating a second messenger pathway in response to an inducer binding to the extracellular portion of these receptors is the subject of U.S. Pat. No. 5,359,046, the entirety of which is incorporated herein by reference. These chimeric receptor molecules comprise three domains in a single protein moiety, namely, a cytoplasmic effector function signaling domain, a transmembrane domain and an extracellular inducer binding domain. The cytoplasmic domain and extracellular domain are not naturally associated together. By mixing and matching extracellular domains with a particular type of cytoplasmic domain, one may transduce a particular signal by employing different inducers that bind to different extracellular binding domain receptors. Additionally, these single molecule receptors have the desired characteristics of binding inducer and transducing a signal without requiring the major histocompatibility complex (MHC) involvement or antigen presentation. Such characteristics make these chimeric receptors ideal in the development of cellular therapies by permitting the directed activity of cells selected for a particular effector function.
To enhance the above technology, it would be desirable to insure that cells expressing these chimeric receptors with effector function are present in the body in sufficient quantity for effective cellular therapy or treatment. This requirement may be met by the proliferation of the cells expressing the chimeric effector function receptor at the site where they would be most advantageous.
The present invention provides a strategy that consists of further engineering cells, including those expressing chimeric effector function receptors such that they are capable of proliferating in the body in an inducer molecule driven fashion and, in addition, may be growth factor independent.
There is also a general need in the field for a variety of therapeutic cells to proliferate in vivo either when they have homed to or are transplanted to the proper site or in response to an administered inducer molecule. The present invention provides a method to direct cell proliferation in this manner.